Trodelvy (sacituzumab govitecan-hziy)

The efficacy results showed a significantly greater clinical benefit with sacituzumab govitecan compared to standard chemotherapy in patients with triple-negative breast cancer. This drug will become a treatment of substantial impact in future treatment guidelines for this type of cancer.

Our systematic review and meta-analysis confirmed that SG confers good clinical activity in certain solid tumor types and was tolerable with minimal adverse events. The potential utility of UGT1A1*28 genotyping in predicting clinical response and outcomes could not be determined due to the limited number of studies with available UGT1A1 genotype data.

P2, N=129, Not yet recruiting, Fundación GECP | Trial completion date: Jun 2031 --> Nov 2031 | Trial primary completion date: Jun 2031 --> Nov 2031

P4, N=25, Completed, Gilead Sciences | Enrolling by invitation --> Completed | N=200 --> 25

P2, N=348, Recruiting, West German Study Group | Not yet recruiting --> Recruiting

P2, N=23, Not yet recruiting, University of California, Irvine

P1/2, N=56, Active, not recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Recruiting --> Active, not recruiting

For the treatment of breast cancer, there are three ADCs approved for breast cancer treatment: Trastuzumab emtansine (T-DM1), Trastuzumab Deruxtecan (T-Dxd) targeting HER-2, and Sacituzumab Govitecan (SG) targeting Trop-2. This review summarizes the efficacy and adverse effects of ADC therapies that have completed or are currently undergoing phase I-III clinical trials. Additionally, it analyzes potential combination strategies to overcome ADC resistance, aiming to provide clinicians with a comprehensive clinical guide to the use of ADCs in breast cancer treatment.

Our data indicate that targeted therapy using e.g., trastuzumab deruxtecan, bicalutamide, pembrolizumab, cetuximab, entrectinib or sacituzumab govitecan might be a promising option especially for a relevant subset of patients with RM-SGC not suitable for salvage surgery. However, evidence from clinical studies regarding response rates to these therapies remains sparse, which underlines the need of multicenter clinical trials.

P1/2, N=54, Recruiting, Icahn School of Medicine at Mount Sinai | Not yet recruiting --> Recruiting

P2, N=20, Not yet recruiting, British Columbia Cancer Agency

In this report we describe the case of a patient with TNBC diagnosed at the metastatic level when the primary breast tumour presented overexpression of ER end PgR. An important tumoral heterogeneity has been described in breast cancer during its natural evolution and for that reason is important to perform metastatic lesions re-biopsy, when feasible, in order to re-evaluate the biological characteristics and define the optimal therapeutic strategy.

Approximately 15% of TNBC patients have a germline mutation in BRCA1 and/or BRCA2, and for these patients, innovative therapeutic options such as olaparib and talazoparib, which are PARP inhibitors, are available. Sacituzumab govitecan (SG) is a humanized monoclonal antibody-drug conjugate directed against the surface antigen of human trophoblastic cells (Trop-2) expressed in approximately 90% of TNBC, coupled with SN-38, the active metabolite of irinotecan, a topoisomerase I inhibitor. Here, we present the case of a woman who was initially diagnosed with localized luminal B breast cancer (ER-positive; HER2-negative) and was treated with curative therapy. However, she later experienced a recurrence with metastatic TNBC (ER-negative/HER2-negative) and received treatment with sacituzumab govitecan, which resulted in prolonged disease control.

P2, N=92, Terminated, Gilead Sciences | Active, not recruiting --> Terminated; Sponsor decision to terminate study.

Knockdown of TROP2 also resulted in decreased expression of vimentin, along with reduced migratory capacity. These findings suggest that TROP2 plays a crucial role in cSCC cell proliferation and migration, and highlight the potential of sacituzumab govitecan as a promising therapeutic option for cSCC.

P3, N=540, Recruiting, Gilead Sciences | Trial completion date: May 2027 --> Jul 2028 | Trial primary completion date: May 2027 --> Jul 2028

Pretreatment [18F]FDG PET/CT-derived biomarkers, namely TMTV and Dmax, have significant prognostic value in patients with mTNBC and HER2-low mBC treated with SG and T-DXd. These biomarkers improve prognostic prediction and may optimize treatment strategies, warranting their clinical use, but larger studies are needed to validate these findings.

P2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Dec 2024 --> Dec 2025

In a real-world cohort of heavily pretreated patients with mTNBC, SG retains its clinical activity. In a subgroup with HER2-low disease, T-DXd continues to demonstrate promising clinical activity after SG, supporting the use of sequential antibody-drug conjugates in this population.

SG represents a promising treatment option for Asian patients with HR+HER2- mBC (ClinicalTrials.gov identifier no. NCT04639986 ).

However, the current ADC, sacituzumab govitecan, fails to overcome the crucial role of adenosine in the suppressive immune microenvironment characteristic of this "cold tumor"...Thus, it kills tumor cells with cytotoxic drugs, comprehensively regulates immunosuppression, and restores a durable immune response. This study proposes an antibody-polymeric drug complex with immunomodulatory and immunoagonist roles, offering new insights into TNBC treatment.

Sacituzumab Govitecan (SG) is an antibody-drug conjugate (ADC) comprised of an anti-Trop-2 IgG1 molecule conjugated to SN-38, the active metabolite of irinotecan, via a pH-sensitive hydrolysable linker. The most common AEs were neutropenia, diarrhea, nausea, fatigue, alopecia, and anemia. This review outlines AE management recommendations for SG based on clinical trial protocols and Canadian guidelines, incorporating treatment delay, dose reductions, and the use of prophylactic and supportive medications.

P2, N=252, Recruiting, Guangdong Provincial People's Hospital | Initiation date: Jan 2024 --> Sep 2024

P1/2, N=76, Not yet recruiting, MedSIR

P2, N=42, Recruiting, Grupo Espanol de Tumores Neuroendocrinos | Not yet recruiting --> Recruiting

P3, N=520, Recruiting, Gilead Sciences | Not yet recruiting --> Recruiting

P1/2, N=645, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting | Trial completion date: Nov 2027 --> May 2026

P2, N=40, Recruiting, The University of Texas Health Science Center at San Antonio | Trial completion date: Feb 2025 --> Aug 2026 | Trial primary completion date: Aug 2024 --> Feb 2026

SG RP2D was established as 10 mg/kg in Japanese patients. SG showed efficacy in Japanese patients with previously treated mTNBC, a manageable safety profile, and no new safety signals, consistent with the previous ASCENT study.

P2, N=92, Active, not recruiting, Gilead Sciences | Trial completion date: Jan 2025 --> Oct 2024

P3, N=696, Active, not recruiting, Gilead Sciences | Trial completion date: Oct 2024 --> Jul 2025 | Trial primary completion date: Oct 2024 --> Jul 2025

P1/2, N=173, Completed, Arcus Biosciences, Inc. | Active, not recruiting --> Completed

P3, N=443, Active, not recruiting, Gilead Sciences | Recruiting --> Active, not recruiting

P1/2, N=135, Active, not recruiting, Gilead Sciences | Recruiting --> Active, not recruiting

In MBC, ADCs have expanded treatment options but their sequential use requires further study. Evidence suggests that sequencing ADCs with similar payloads is ineffective, though current data are inconclusive. More research is needed to optimize treatment strategies, including potential combination therapies.

These novel combinations are revolutionizing the treatment standard for metastatic urothelial carcinoma and necessitate a new approach to managing side effects.

The third-generation antibody-drug conjugates (ADC), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), recently obtained approval for metastatic breast cancer treatment across various subtypes and therapeutic contexts. 95.7% of the protocol-specified, therapeutic dose was administered for T-DXd and 89.6% for SG. Overall, this indicates good feasibility, tolerability, and effectiveness of ADC therapies in the real-world setting.

P2, N=827, Recruiting, Gilead Sciences | Trial completion date: Jul 2026 --> Jun 2030 | Trial primary completion date: Jul 2024 --> Jun 2030

P1, N=26, Completed, The University of Texas Health Science Center at San Antonio | Active, not recruiting --> Completed | Trial completion date: Jul 2024 --> Mar 2024

P1/2, N=31, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Not yet recruiting --> Recruiting

Utilizing multiomic analyses and experimental validation, this work identifies a pivotal role for the USP10/B7-H4 proteolytic axis in mediating the interplay between tumor immune responses and ADC efficacy, particularly for sacituzumab govitecan (SG) in treating triple negative breast cancers (TNBCs)...In preclinical TNBC models, suppression of USP10/B7-H4 proteolytic axis is effective in increasing SG killing efficacy and reducing tumor growth, especially for the tumors with the USP10high/B7-H7high signature. Collectively, these findings uncover a novel strategy for targeting the immunosuppressive molecule B7-H4 for cancer therapy.

With a manageable toxicity profile, SG represents a significant advancement in the treatment landscape for this patient population. However, further research is essential to optimize its application and establish long-term benefits.